This is a request for support of the fourth meeting in a highly successful series of Gordon Research Conferences on Cartilage Biology and Pathology, to be held at the Les Diablerets, Switzerland, June 7-12, 2009. Building on the success of the previous conferences, the meeting brings together outstanding senior and junior scientists and advanced graduate students and postdoctoral fellows for a 4.5 -day program of formal presentations, informal discussions and interactions and poster presentations. The participants share an interest in cartilage biology and pathology but represent a broad range of disciplines, including developmental and evolutionary biology, extracellular matrix biochemistry, cell and molecular biology, mechanobiology and tissue engineering, pathology, genetics, and orthopedics. Cartilage is a remarkable tissue that has several crucial functions. During skeletal development, models of the future bones are mostly made of cartilage. By a complex series of cellular processes these cartilage models are replaced by bone marrow and bone tissue, except towards the ends where a region of cartilage remains as growth plate cartilage, and at the very end, where a layer of cartilage serves as a slippery, shock-absorbing structure to allow bones to freely move where they meet in joints. Finally, a shock-absorbing and elastic layer of specialized cartilage between the vertebral bodies in the spine allows bending and twisting of the body. Growth plate cartilage in long bones and thin layers of cartilage between bones at the base of the skull are crucial for the increase in length of long bones during childhood and adolescence and the enlargement of the skull needed to accommodate the growing brain. When cartilage fails the consequences can be severe, ranging from death around birth to reduced growth of the skeleton or degenerative joint and spine disease in the aging adult. Several decades of research into cartilage and its disorders have led to identification of predisposing factors and cellular mechanisms of disease. Great strides have also been made in the understanding of genes and molecular mechanisms that regulate formation of cartilage-forming cells, the functions of growth plate cartilage and the formation of joints. At the same time advances in stem cell biology and tissue engineering is opening the door to the possibility that degenerating cartilage can one day be repaired or stimulated to regenerate. However, much remains to be understood before knowledge-based therapeutic strategies can be developed to prevent or slow down progression of osteoarthritis and degenerative changes in the spine, treat the consequences of mutations that affect growth plate function or repair/regenerate defective cartilage. The aim of the meeting is to stimulate interdisciplinary research to advance progression towards these goals.